Project Summary This proposed five-year development period will be used for research and training activities that will give Dr. Brennan the skills and experience necessary to become an independent investigator. Dr. Brennan?s long-term career goals are to use high volume, high variety and high velocity large-scale datasets to provide evidence for the development of effective policies, programs and interventions to improve management and clinical outcomes of patients with chronic communicable (i.e. HIV and tuberculosis) and non-communicable diseases (i.e. diabetes, cardiovascular disease and chronic kidney disease) at a national level in South Africa. Although Dr. Brennan is a clinical epidemiologist and methodologist by training, she recognizes the need and has a strong desire to acquire applied data science and ?Big Data? analytical skills to stay competitive in the field. Building on her already strong background in quantitative data analysis, Dr. Brennan has proposed a training plan to develop skills in novel applied data science methods to deal with large-scale data sets, primary data collection, data validation and epidemiological approaches to causal inference. In addition, she has proposed training in the clinical monitoring, diagnosis, treatment and management of metabolic and cardiovascular conditions. The training plan will involve formal coursework, directed readings on specific topics, and strong mentorship from experts in the field of metabolic disorders and HIV, domestically and internationally. The proposed research will combine analyses of existing data from the National Health Laboratory Services in South Africa, the sole provider for public sector labs, and patient-level data from a primary health care clinic in the government sector. Upon successful completion of Dr. Brennan?s K01 award she will have started to build an invaluable resource to assess the burden of non-communicable chronic diseases in South Africa. Dr. Brennan?s high impact research is not only generalizable to other low- and middle-income countries, but would also be relevant to high-income countries where similar populations exist, but not in the numbers necessary to assess meaningful associations and interactions between desired exposures and outcomes. Through the creation of this resource, in addition to further strengthening her quantitative skill set and clinical knowledge of diabetes, Dr. Brennan will have developed competency as an independent researcher capable of securing R- series NIH funding.